DESCRIPTION (from the principal investigator's proposal): The long-term goals of these studies are to understand how optic nerves and other axons of the central nervous system form accurate synaptic connections during development and how optic nerves of adult humans might successfully respond to injury and regenerate. For this, the adult goldfish is used as a model because its optic nerve can regenerate to reform a precise projection into the brain while utilizing impulse activity and other cellular cues common to mammalian development. Four specific aims are proposed. The first uses nanoliter injections of a fluorescent tracer, DiI, to label axons from neighboring retinal ganglion cells visualized in tectal whole mounts. These are examined at various times during regeneration and after various pharmacologic manipulations such as blockade of impulse activity and stimulation of neurotransmitter receptors to determine the structural changes and events associated with the reformation of fine retinotopic order. The second aim uses similar labeling but visualizes regenerating axons in the living fish for 6 h to 4 d to understand the dynamic events associated with regeneration and to perform real time pharmacological experiments on growing axons for the first time in an adult vertebrated. The third aim will use retinal explants in culture to compare the dynamics and pharmacological responses of optic axons regenerating in the isolation of tissue culture with that seen in the animal. The fourth aim is to determine the pattern and amount of activity expressed by regenerating optic fibers using electrophysiological recording since this activity may be important for determining synaptic connections and since the information will be needed to interpret and perform the preceding experiments.